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Background and Hypothesis: The glymphatic system (GS), a brain waste clearance pathway, is disrupted in various neurodegenerative and vascular diseases. As schizophrenia shares clinical characteristics with these conditions, we hypothesized GS disruptions in patients with schizophrenia spectrum disorder (SCZ-SD), reflected in increased brain macromolecule (MM) and decreased diffusion-tensor-image-analysis along the perivascular space (DTI-ALPS) index., Study Design: Forty-seven healthy controls (HCs) and 103 patients with SCZ-SD were studied. Data included 135 proton magnetic resonance spectroscopy (1H-MRS) sets, 96 DTI sets, with 79 participants contributing both. MM levels were quantified in the dorsal-anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and dorsal caudate (point resolved spectroscopy, echo-time = 35ms). Diffusivities in the projection and association fibers near the lateral ventricle were measured to calculate DTI-ALPS indices. General linear models were performed, adjusting for age, sex, and smoking. Correlation analyses examined relationships with age, illness duration, and symptoms severity., Study Results: MM levels were not different between patients and HCs. However, left, right, and bilateral DTI-ALPS indices were lower in patients compared with HCs (P < .001). In HCs, age was positively correlated with dACC MM and negatively correlated with left, right, and bilateral DTI-ALPS indices (P < .001). In patients, illness duration was positively correlated with dACC MM and negatively correlated with the right DTI-ALPS index (P < .05). In the entire population, dACC MM and DTI-ALPS indices showed an inverse correlation (P < .01)., Conclusions: Our results suggest potential disruptions in the GS of patients with SCZ-SD. Improving brain's waste clearance may offer a potential therapeutic approach for patients with SCZ-SD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Rationale and Objectives: The mechanism of comorbidity between alcohol dependence and depressive disorders are not well understood. This study investigated differences in the brain function of alcohol-dependent patients with and without depression by performing functional connectivity analysis using resting-state functional magnetic resonance imaging., Materials and Methods: A total of 29 alcohol-dependent patients with depression, 31 alcohol-dependent patients without depression and 31 healthy control subjects were included in this study. The resting-state functional connectivity between the amygdala and the whole brain was compared among the three groups. Additionally, we examined the correlation between functional connectivity values in significantly different brain regions and levels of alcohol dependence and depression., Results: The resting-state functional connectivity between the left amygdala and the right caudate nucleus was decreased in alcohol-dependent patients. Additionally, the resting-state functional connectivity of the right amygdala with the right caudate nucleus, right transverse temporal gyrus, right temporal pole: superior temporal gyrus were also decreased. In alcohol-dependent patients with depression, not only was functional connectivity between the above brain regions significantly decreased, but so was functional connectivity between the right amygdala and the left middle temporal gyrus. Also, there was no significant correlation between the resting-state functional connectivity values in statistically significant brain regions and the levels of alcohol dependence and depression., Conclusion: The impairment of the functional connectivity of the amygdala with caudate nucleus and partial temporal lobe may be involved in the neural mechanism of alcohol dependence comorbidity depressive disorders., Competing Interests: Declaration of Competing Interest The authors have declared that there are no conflicts of interest in relation to the subject of this study., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Having multiple previous generations with depression in the family increases offspring risk for psychopathology. Parental depression has been associated with smaller subcortical brain volumes in their children, but whether two prior generations with depression is associated with further decreases is unclear., Methods: Using two independent cohorts, 1) a Three-Generation Study (TGS, N = 65) with direct clinical interviews of adults and children across all three generations, and 2) the Adolescent Brain Cognitive Development Study (ABCD, N = 10,626) of 9-10 year-old children with family history assessed by a caregiver, we tested whether having more generations of depression in the family was associated with smaller subcortical volumes (using structural MRI)., Results: In TGS, caudate, pallidum and putamen showed decreasing volumes with higher familial risk for depression. Having a parent and a grandparent with depression was associated with decreased volume compared to having no familial depression in these regions. Putamen volume was associated with depression at eight-year follow-up. In ABCD, smaller pallidum and putamen were associated with family history, which was driven by parental depression, regardless of grandparental depression., Limitations: Discrepancies between cohorts could be due to interview type (clinical or self-report) and informant (individual or common informant), sample size or age. Future analyses of follow-up ABCD waves will be able to assess whether effects of grandparental depression on brain markers become more apparent as the children enter young adulthood., Conclusions: Basal ganglia regional volumes are significantly smaller in offspring with a family history of depression in two independent cohorts., Competing Interests: Declaration of competing interest Dr. Weissman receives funds from NIMH and Columbia University Institute for Developmental Sciences and book royalties from Perseus Press and Oxford Press. Dr. Posner has received research support from Takeda (formerly Shire) and Aevi Genomics and consultancy fees from Innovative Science and AlphaSights. None of these present a conflict of interest with or have influenced the research presented in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/objectives: This systematic review and meta-analysis aimed to investigate the role of magnetic susceptibility (χ) in deep gray matter (DGM) structures, including the putamen (PUT), globus pallidus (GP), caudate nucleus (CN), and thalamus, in the most common types of multiple sclerosis (MS) and relapsing-remitting MS (RRMS), using quantitative susceptibility mapping (QSM)., Methods: The literature was systematically reviewed up to November 2023, adhering to PRISMA guidelines. This study was conducted using a random-effects model to calculate the standardized mean difference (SMD) in QSM values between patients with RRMS and healthy controls (HCs). Publication bias and risk of bias were also assessed., Results: Nine studies involving 1074 RRMS patients with RRMS and 640 HCs were included in the meta-analysis. The results showed significantly higher QSM (χ) values in the PUT (SMD = 0.40, 95% confidence interval [CI] = 0.22-0.59, p = .000), GP (SMD = 0.60, 95% CI = 0.50-0.70, p = .00), and CN (SMD = 0.40, 95% CI = 0.15-0.66, p = .005) of RRMS patients compared to HCs. However, there were no significant differences in the QSM values in the thalamus between patients with RRMS and HCs (SMD = -0.33, 95% CI -0.67-0.01, p = .026). Age- and sex-based subgroup analysis demonstrated that younger patients (< 40 years) in the PUT, GP, and CN groups and larger male populations (> 25%) in the PUT and GP groups had more significant χ. Interestingly, thalamic QSM values were found to decrease in RRMS patients over 40 years of age and in higher male populations. Sex-based subgroup analysis indicated higher iron levels in the PUT and GP of RRMS patients regardless of sex. QSM values were higher in certain brain regions (PUT, GP, and CN) during the early stages (disease duration < 9.6 years) of RRMS, but lower in the thalamus during the later stages (disease duration > 9.6 years) than HCs., Discussion/conclusion: QSM may serve as a biomarker for understanding χ value alterations such as iron dysregulation and its contribution to neurodegeneration in RRMS, especially in the basal ganglia nuclei including PUT, GP, and CN., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

The caudate nucleus is a part of the striatum, and striatal hyperdopaminergia is considered central to the pathophysiology of schizophrenia. How caudate volume is affected in schizophrenia and what role antipsychotics play remains unclear. In early-onset schizophrenia (EOS), where psychosis emerges during a neurodevelopmentally critical phase, the caudate may exhibit a heightened vulnerability to the effects of antipsychotic medications. We hypothesized effects of both antipsychotic medication use and age of onset on caudate in schizophrenia. We included adult patients with EOS (n = 83) and adult-onset schizophrenia (AOS) (n = 246), adult healthy controls (HC, n = 774), adolescent patients with non-affective psychosis (n = 56) and adolescent HC (n = 97). We obtained T1-weighted MRI scans using a 1.5T Siemens scanner and General Electric 3T scanners. In our main analysis, we tested for main and interaction effects of diagnosis and current antipsychotic medication use on caudate volume. Adult patients with EOS (p < 0.001) and AOS (p = 0.002) had both larger caudate than HC. Age of onset (EOS/AOS) interacted with antipsychotic use (p = 0.004) which was associated with larger caudate in EOS (p < 0.001) but not in AOS (p = 0.654). Conversely, among medicated patients only, EOS had larger caudate than AOS (p < 0.001). No other subcortical structures showed differences between medicated EOS and AOS. Medicated adolescent patients with non-affective psychosis and medicated adult patients with EOS showed similar caudate volumes. The results may indicate a schizophrenia-related and a medication-induced caudate increase, the latter restricted to patients with EOS and possibly occurring already in adolescence shortly after disease onset., (© 2024. The Author(s).)

The complexity of brain activity reflects its ability to process information, adapt to environmental changes, and transition between states. However, it remains unclear how schizophrenia (SZ) affects brain activity complexity, particularly its dynamic changes. This study aimed to investigate the abnormal patterns of brain activity complexity in SZ, their relationship with cognitive deficits, and the impact of antipsychotic medication. Forty-four drug-naive first-episode (DNFE) SZ patients and thirty demographically matched healthy controls (HC) were included. Functional MRI-based sliding window analysis was utilized for the first time to calculate weighted permutation entropy to characterize complex patterns of brain activity in SZ patients before and after 12 weeks of risperidone treatment. Results revealed reduced complexity in the caudate, putamen, and pallidum at baseline in SZ patients compared to HC, with reduced complexity in the left caudate positively correlated with Continuous Performance Test (CPT) and Category Fluency Test scores. After treatment, the complexity of the left caudate increased. Regions with abnormal complexity showed decreased functional connectivity, with complexity positively correlated with connectivity strength. We observed that the dynamic complexity of the brain exhibited the characteristic of spontaneous, recurring "complexity drop", potentially reflecting transient state transitions in the resting brain. Compared to HC, patients exhibited reduced scope, intensity, and duration of complexity drop, all of which improved after treatment. Reduced duration was negatively correlated with CPT scores and positively with clinical symptoms. The results suggest that abnormalities in brain activity complexity and its dynamic changes may underlie cognitive deficits and clinical symptoms in SZ patients. Antipsychotic treatment partially restores these abnormalities, highlighting their potential as indicators of treatment efficacy and biomarkers for personalized therapy., (© 2024. The Author(s).)

Brain iron increases in several neurodegenerative diseases are associated with disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron, systemic iron and inflammatory status. Brain magnetic resonance imaging (MRI) scans and blood plasma samples were collected from cognitively healthy females (n = 176, mean age = 61.4 ± 4.5 years, age range = 28-72 years) and males (n = 152, mean age = 62.0 ± 5.1 years, age range = 32-74 years). Regional brain iron was quantified using quantitative susceptibility mapping. To assess systemic iron, haematocrit, ferritin and soluble transferrin receptor were measured, and total body iron index was calculated. To assess systemic inflammation, C-reactive protein (CRP), neutrophil:lymphocyte ratio (NLR), macrophage colony-stimulating factor 1 (MCSF), interleukin 6 (IL6) and interleukin 1β (IL1β) were measured. We demonstrated that iron levels in the right hippocampus were higher in males compared with females, while iron in the right caudate was higher in females compared with males. There were no significant associations observed between subcortical iron levels and blood markers of iron and inflammatory status indicating that such blood measures are not markers of brain iron. These results suggest that brain iron may be regulated independently of blood iron and so directly targeting global iron change in the treatment of neurodegenerative disease may have differential impacts on blood and brain iron., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Cognitive dysfunction constitutes a core characteristic of schizophrenia spectrum disorders (SZ). Specifically, deficits in updating generative models (i.e., cognitive flexibility) and shielding against distractions (i.e., cognitive stability) are considered critical contributors to cognitive impairment in these patients. Here, we examined the structural integrity of frontostriatal networks and their associations with reduced cognitive stability and flexibility in SZ patients. In a sample of 21 patients diagnosed with SZ and 22 healthy controls, we measured gray matter volume (GMV) using structural MRI. Further, cognitive stability and flexibility were assessed using a switch-drift paradigm, quantifying the successful ignoring of distracters and detection of rule switches. Compared to controls, patients showed significantly smaller GMV in the whole brain and three predefined regions of interest: the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), and caudate nucleus (CN). Notably, GMV in these areas positively correlated with correct rule-switch detection but not with ignoring rule-compatible drifts. Further, the volumetric differences between SZ patients and controls were statistically explainable by considering the behavioral performance in the switch-drift task. Our results indicate that morphological abnormalities in frontostriatal networks are associated with deficient flexibility in SZ patients and highlight the necessity of minimizing neurodevelopmental and progressive brain atrophy in this population., (© 2024 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

The role of dopamine in the pathophysiology of gambling disorder (GD) remains incompletely understood, with disparate research findings concerning presynaptic and postsynaptic structures and dopaminergic synthesis. The aim of this study was to investigate potential correlations between striatal dopamine transporter (DAT) lateralization and asymmetry index, as assessed by 123 I-FP-CIT SPECT, and temperamental traits, as measured by Cloninger's Temperament and Character Inventory (TCI), in GD subjects. Significant associations were found between DAT binding asymmetries in the caudate and putamen and the temperamental dimensions of harm avoidance and novelty seeking. Specifically, high novelty seeking scores correlated with increased DAT binding in the left caudate relative to the right, whereas higher harm avoidance scores corresponded to increased DAT binding in the right putamen relative to the left. These observations potentially imply that the asymmetry in DAT expression in the basal ganglia could be an outcome of hemispheric asymmetry in emotional processing and behavioural guidance. In summary, our study provides evidence supporting the relationship between DAT asymmetries, temperamental dimensions and GD. Future investigations could be directed towards examining postsynaptic receptors to gain a more comprehensive understanding of dopamine's influence within the basal ganglia circuit in disordered gambling. If confirmed in larger cohorts, these findings could have substantial implications for the tailoring of individualized neuromodulation therapies in the treatment of behavioural addictions., Competing Interests: Declarations G.M. has been a consultant and a speaker and has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Recordati. J. E. G. has received research grants from Janssen, Boehringer Ingelheim, and Biohaven Pharmaceuticals. He receives yearly compensation from Springer Publishing for acting as Editor-in Chief of the Journal of Gambling Studies and has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, and McGraw Hill. The other Authors have nothing to declare., (© 2024. The Author(s).)

Primates must adapt to changing environments by optimizing their behavior to make beneficial choices. At the core of adaptive behavior is the orbitofrontal cortex (OFC) of the brain, which updates choice value through direct experience or knowledge-based inference. Here, we identify distinct neural circuitry underlying these two separate abilities. We designed two behavioral tasks in which two male macaque monkeys updated the values of certain items, either by directly experiencing changes in stimulus-reward associations, or by inferring the value of unexperienced items based on the task's rules. Chemogenetic silencing of bilateral OFC combined with mathematical model-fitting analysis revealed that monkey OFC is involved in updating item value based on both experience and inference. In vivo imaging of chemogenetic receptors by positron emission tomography allowed us to map projections from the OFC to the rostromedial caudate nucleus (rmCD) and the medial part of the mediodorsal thalamus (MDm). Chemogenetic silencing of the OFC-rmCD pathway impaired experience-based value updating, while silencing the OFC-MDm pathway impaired inference-based value updating. Our results thus demonstrate dissociable contributions of distinct OFC projections to different behavioral strategies, and provide new insights into the neural basis of value-based adaptive decision-making in primates., (© 2024. The Author(s).)

Temporal discounting, in which the recipient of a reward perceives the value of that reward to decrease with delay in its receipt, is associated with impulsivity and psychiatric disorders such as depression. Here, we investigate the role of the serotonin 5-HT 4 receptor (5-HT 4 R) in modulating temporal discounting in the macaque dorsal caudate nucleus (dCDh), the neurons of which have been shown to represent temporally discounted value. We first mapped the 5-HT 4 R distribution in macaque brains using positron emission tomography (PET) imaging and confirmed dense expression of 5-HT 4 R in the dCDh. We then examined the effects of a specific 5-HT 4 R antagonist infused into the dCDh. Blockade of 5-HT 4 R significantly increased error rates in a goal-directed delayed reward task, indicating an increase in the rate of temporal discounting. This increase was specific to the 5-HT 4 R blockade because saline controls showed no such effect. The results demonstrate that 5-HT 4 Rs in the dCDh are involved in reward-evaluation processes, particularly in the context of delay discounting, and suggest that serotonergic transmission via 5-HT 4 R may be a key component in the neural mechanisms underlying impulsive decisions, potentially contributing to depressive symptoms., (© 2024. The Author(s).)

Suicide is the second leading cause of death in youth, and depression is a strong proximal predictor of adolescent suicide. It is important to identify psychological factors that may protect against suicide ideation in depressed adolescents. Self-compassion may be such a factor. Converging evidence indicates the inverse association between self-compassion and suicide ideation, but the neural mechanisms underlying their link remain unknown. Because self-referential caudate activity is associated with both self-compassion and suicide ideation, its functional connectivity might explain their relationship. In this study, we examined the relationship between self-compassion and caudate functional connectivity during self-appraisals, a typical self-referential paradigm, and their associations with suicide ideation in both depressed and healthy youth. In the scanner, 79 depressed youth and 36 healthy controls evaluated, from various perspectives, whether phrases they heard were self-descriptive. Self-compassion and suicide ideation were rated with self-report and interview-based measures. We found that self-compassion was associated with stronger left caudate functional connectivity with bilateral posterior superior temporal sulcus/temporoparietal junction, the left middle temporal gyrus (MTG), and the left middle occipital gyrus during positive versus negative self-appraisals. Stronger left caudate connectivity with the left MTG explained the association between higher self-compassion and lower suicide ideation, even controlling for non-suicide ideation depression severity, anxiety severity, and non-suicidal self-injurious behavior. The findings suggest that the left caudate to MTG connectivity during positive versus negative self-referential processing could be a biomarker to be targeted by neural stimulation interventions for reducing suicide ideation in depressed youth, combined with self-compassion interventions., (© 2024. The Author(s).)

It is of vital importance to establish an objective and reliable model to facilitate the early diagnosis and intervention of internet gaming disorder (IGD). A total of 133 patients with IGD and 110 healthy controls (HCs) were included. We extracted radiomic features of subcortical structures in high-resolution T1-weighted MRI. Different combinations of four feature selection methods (analysis of variance, Kruskal-Wallis, recursive feature elimination and relief) and ten classification algorithms were used to identify the most robust combined models for distinguishing IGD patients from HCs. Furthermore, a nomogram incorporating radiomic signatures and independent clinical factors was developed. Calibration curve and decision curve analyses were used to evaluate the nomogram. The combination of analysis of variance selector and logistic regression classifier identified that the radiomic model constructed with 20 features from the right caudate nucleus and amygdala showed better IGD screening performance. The radiomic model produced good areas under the curves (AUCs) in the training, validation and test cohorts (AUCs of 0.961, 0.903 and 0.895, respectively). In addition, sex, internet addiction test scores and radiomic scores were included in the nomogram as independent risk factors for IGD. Analysis of the correction curve and decision curve showed that the clinical-radiomic model has good reliability (C-index: 0.987). The nomogram incorporating radiomic features of subcortical structures and clinical characteristics achieved satisfactory classification performance and could serve as an effective tool for distinguishing IGD patients from HCs., Competing Interests: Declaration of competing interest The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear., Methods: The current study combined resting-state fMRI data from patients with AN ( n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength - specifically between the anterior caudate and dlPFC - differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality., Results: Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity ( p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri ( p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex ( p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality., Conclusions: Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

Background and Objectives: A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach., Methods: For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures., Results: We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]- p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR- p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR- p ≤ 0.016) and thalamic (FDR- p ≤ 0.048) layers, and in the outer caudate layer (FDR- p = 0.024). They showed lower R2* values in the outer cortical layer (FDR- p = 0.003) and in the outer thalamic layer (FDR- p = 0.046) and higher R2* values in all 3 caudate layers (FDR- p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR- p ≤ 0.002) and thalamic (FDR- p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR- p = 0.005), thalamic R2* (FDR- p = 0.004), and caudate MTR (FDR- p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR- p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR- p = 0.040). No correlations with choroid plexus volume were found., Discussion: CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.

We used a virtual navigation paradigm in a city environment to assess neuroanatomical correlates of cognitive deficits in schizophrenia spectrum disorders (SSD). We studied a total of N = 36 subjects: 18 with SSD and 18 matched unaffected controls. Participants completed 10 rapid, single-trial navigation tasks within the virtual city while undergoing functional magnetic resonance imaging (fMRI). All trials tested ability to find different targets seen earlier, during the passive viewing of a path around different city blocks. SSD patients had difficulty finding previously-encountered targets, were less likely to find novel shortcuts to targets, and more likely to attempt retracing of the path observed during passive viewing. Based on a priori region-of-interest analyses, SSD participants had hyperactivation of the left hippocampus when passively viewing turns, hyperactivation of the left caudate when finding targets, and hypoactivation of a focal area of the dorsolateral prefrontal cortex when targets were initially shown during passive viewing. We propose that these brain-behaviour relations may bias or reinforce stimulus-response navigation approaches in SSD and underlie impaired performance when allocentric spatial memory is required, such as when forming efficient shortcuts. This pattern may extend to more general cognitive impairments in SSD that could be used to design remediation strategies., Competing Interests: Declaration of competing interest Dr. Foussias has been involved in research sponsored by Medicure Inc., and Neurocrine Bioscience, has received consultant fees from Roche, and has received speaker fees from Roche, Lundbeck, and Novartis. Dr. Wong is a scientific consultant to Lucid psycheceuticals, a subsidiary of FSD Pharma Inc. The other authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The purpose of this study was to examine N-acetyl aspartate (NAA)/creatine (Cr) and glutamate, glutamine, and gamma-aminobutyric acid complex (Glx)/Cr levels in patients with obsessive compulsive disorder (OCD) and healthy controls' orbitofrontal cortex (OFC) and caudate nucleus (CN) by proton magnetic resonance spectroscopy (1H-MRS) method and to investigate their relationship with oxidative stress markers glutathione peroxidase (GPx) and superoxide dismutase (SOD)., Methods: This study included patients with OCD (n = 25) and healthy controls (n = 25) ranging in age from 18 to 65. We used the ELISA method to evaluate serum SOD and GPx levels. Levels of NAA/Cr and Glx/Cr in the orbitofrontal cortex and caudate nucleus were measured using the 1H-MRS method., Results: Our study did not detect statistically significant differences in the orbitofrontal cortex Glx/Cr and NAA/Cr levels between the OCD patients and the control group. OCD patients exhibited a decrease in NAA/Cr levels, consistent with impaired neuronal integration, and an increase in Glx/Cr levels, consistent with hyperactivation, in the caudate nucleus compared to the control group. We observed a negative correlation between NAA/Cr levels in the caudate nucleus and the levels of SOD and GPx., Conclusions: Our study is the first to assess CN and OFC together in OCD patients using 3 T MR, investigating the relationship between neurometabolite concentrations and oxidative stress parameters. The negative correlation we observed between NAA/Cr levels and SOD and GPx in the caudate nucleus suggests that increased oxidative stress in this brain region in OCD patients may contribute to impaired neuronal integration and functionality., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The striatum receives projections from multiple regions of the cerebral cortex consistent with the role of the basal ganglia in diverse motor, affective, and cognitive functions. Within the striatum, the caudate receives projections from association cortex, including multiple distinct regions of prefrontal cortex. Building on recent insights about the details of how juxtaposed cortical networks are specialized for distinct aspects of higher-order cognition, we revisited caudate organization using within-individual precision neuroimaging initially in two intensively scanned individuals (each scanned 31 times). Results revealed that the caudate has side-by-side regions that are coupled to at least five distinct distributed association networks, paralleling the organization observed in the cerebral cortex. We refer to these spatial groupings of regions as striatal association megaclusters. Correlation maps from closely juxtaposed seed regions placed within the megaclusters recapitulated the five distinct cortical networks, including their multiple spatially distributed regions. Striatal association megaclusters were explored in 15 additional participants (each scanned at least 8 times), finding that their presence generalizes to new participants. Analysis of the laterality of the regions within the megaclusters further revealed that they possess asymmetries paralleling their cortical counterparts. For example, caudate regions linked to the language network were left lateralized. These results extend the general notion of parallel specialized basal ganglia circuits with the additional discovery that, even within the caudate, there is fine-grained separation of multiple distinct higher-order networks that reflects the organization and lateralization found in the cerebral cortex. NEW & NOTEWORTHY An individualized precision neuroimaging approach reveals juxtaposed zones of the caudate that are coupled with five distinct networks in association cortex. The organization of these caudate zones recapitulates organization observed in the cerebral cortex and extends the notion of specialized basal ganglia circuits.

Background: The neurobiological basis of delusional disorder is less explored through neuroimaging techniques than in other psychotic disorders. This study aims to provide information about the neural origins of delusional disorder (DD) by examining the neuroanatomical features of some basal nuclei with magnetic resonance imaging (MRI) texture analysis., Materials and Methods: Twenty DD patients and 20 healthy individuals were included in the study. Globus pallidus, putamen, and caudate nuclei were selected individually with a region of interest (ROI) on the axial MRI images. The entire texture analysis algorithm applied to all selected ROIs was done with an in-house software. Nuclei on both sides were taken as separate samples., Results: There were no significant differences between groups in terms of age and gender. The average "mean, median and maximum" values of all three nuclei were decreased in DD patients. The small putamen area and the differences detected in different tissue parameters for all three nuclei in delusional disorder patients indicate that they differ in delusional disorder from normal controls (p < 0.05)., Conclusion: The differences detected in the texture parameters for all three nuclei indicate that there is something different in the DD from in the normal controls. Neuroimaging studies with larger samples and different techniques in the future may shed light on the etiology of delusional disorder.

Moral judgements about people based on their actions is a key component that guides social decision making. It is currently unknown how positive or negative moral judgments associated with a person's face are processed and stored in the brain for a long time. Here, we investigate the long-term memory of moral values associated with human faces using simultaneous EEG-fMRI data acquisition. Results show that only a few exposures to morally charged stories of people are enough to form long-term memories a day later for a relatively large number of new faces. Event related potentials (ERPs) showed a significant differentiation of remembered good vs bad faces over centerofrontal electrode sites (value ERP). EEG-informed fMRI analysis revealed a subcortical cluster centered on the left caudate tail (CDt) as a correlate of the face value ERP. Importantly neither this analysis nor a conventional whole-brain analysis revealed any significant coding of face values in cortical areas, in particular the fusiform face area (FFA). Conversely an fMRI-informed EEG source localization using accurate subject-specific EEG head models also revealed activation in the left caudate tail. Nevertheless, the detected caudate tail region was found to be functionally connected to the FFA, suggesting FFA to be the source of face-specific information to CDt. A further psycho-physiological interaction analysis also revealed task-dependent coupling between CDt and dorsomedial prefrontal cortex (dmPFC), a region previously identified as retaining emotional working memories. These results identify CDt as a main site for encoding the long-term value memories of faces in humans suggesting that moral value of faces activates the same subcortical basal ganglia circuitry involved in processing reward value memory for objects in primates., (© 2024. The Author(s).)

Background: Intrastriatal delivery of potential therapeutics in Huntington's disease (HD) requires sufficient caudate and putamen volumes. Currently, volumetric magnetic resonance imaging is rarely done in clinical practice, and these data are not available in large research cohorts such as Enroll-HD., Objective: The objective of this study was to investigate whether predictive models can accurately classify HD patients who exceed caudate and putamen volume thresholds required for intrastriatal therapeutic interventions., Methods: We obtained and merged data for 1374 individuals across three HD cohorts: IMAGE-HD, PREDICT-HD, and TRACK-HD/TRACK-ON. We imputed missing data for clinical variables with >72% non-missing values and used the model-building algorithm BORUTA to identify the 10 most important variables. A random forest algorithm was applied to build a predictive model for putamen volume >2500 mm 3 and caudate volume >2000 mm 3 bilaterally. Using the same 10 predictors, we constructed a logistic regression model with predictors significant at P < 0.05., Results: The random forest model with 1000 trees and minimal terminal node size of 5 resulted in 83% area under the curve (AUC). The logistic regression model retaining age, CAG repeat size, and symbol digit modalities test-correct had 85.1% AUC. A probability cutoff of 0.8 resulted in 5.4% false positive and 66.7% false negative rates., Conclusions: Using easily obtainable clinical data and machine learning-identified initial predictor variables, random forest, and logistic regression models can successfully identify people with sufficient striatal volumes for inclusion cutoffs. Adopting these models in prescreening could accelerate clinical trial enrollment in HD and other neurodegenerative disorders when volume cutoffs are necessary enrollment criteria. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

The stomach-derived hormone ghrelin plays not only a role in feeding, starvation, and survival, but it has been suggested to also be involved in the stress response, in neuropsychiatric conditions, and in alcohol and drug use disorders. Mechanisms related to reward processing might mediate ghrelin's broader effects on complex behaviors, as indicated by animal studies and mostly correlative human studies. Here, using a within-subject double-blind placebo-controlled design with intravenous ghrelin infusion in healthy volunteers (n = 30), we tested whether ghrelin alters sensitivity to reward and punishment in a reward learning task. Parameters were derived from a computational model of participants' task behavior. The reversal learning task with monetary rewards was performed during functional brain imaging to investigate ghrelin effects on brain signals related to reward prediction errors. Compared to placebo, ghrelin decreased punishment sensitivity (t = -2.448, p = 0.021), while reward sensitivity was unaltered (t = 0.8, p = 0.43). We furthermore found increased prediction-error related activity in the dorsal striatum during ghrelin administration (region of interest analysis: t-values ≥ 4.21, p-values ≤ 0.044). Our results support a role for ghrelin in reward processing that extends beyond food-related rewards. Reduced sensitivity to negative outcomes and increased processing of prediction errors may be beneficial for food foraging when hungry but could also relate to increased risk taking and impulsivity in the broader context of addictive behaviors., (© 2024. The Author(s).)

The evolutionary history of canids and felids is marked by a deep time separation that has uniquely shaped their behavior and phenotype toward refined predatory abilities. The caudate nucleus is a subcortical brain structure associated with both motor control and cognitive, emotional, and executive functions. We used a combination of three-dimensional imaging, allometric scaling, and structural analyses to compare the size and shape characteristics of the caudate nucleus. The sample consisted of MRI scan data obtained from six canid species (Canis lupus lupus, Canis latrans, Chrysocyon brachyurus, Lycaon pictus, Vulpes vulpes, Vulpes zerda), two canid subspecies (Canis lupus familiaris, Canis lupus dingo), as well as three felids (Panthera tigris, Panthera uncia, Felis silvestris catus). Results revealed marked conservation in the scaling and shape attributes of the caudate nucleus across species, with only slight deviations. We hypothesize that observed differences in caudate nucleus size and structure for the domestic canids are reflective of enhanced cognitive and emotional pathways that possibly emerged during domestication., (© 2024 Wiley Periodicals LLC.)

A crucial step in the clinical adaptation of an AI-based tool is an external, independent validation. The aim of this study was to investigate brain atrophy in patients with confirmed, progressed Huntington's disease using a certified software for automated volumetry and to compare the results with the manual measurement methods used in clinical practice as well as volume calculations of the caudate nuclei based on manual segmentations. Twenty-two patients were included retrospectively, consisting of eleven patients with Huntington's disease and caudate nucleus atrophy and an age- and sex-matched control group. To quantify caudate head atrophy, the frontal horn width to intercaudate distance ratio and the intercaudate distance to inner table width ratio were obtained. The software mdbrain was used for automated volumetry. Manually measured ratios and automatically measured volumes of the groups were compared using two-sample t-tests. Pearson correlation analyses were performed. The relative difference between automatically and manually determined volumes of the caudate nuclei was calculated. Both ratios were significantly different between the groups. The automatically and manually determined volumes of the caudate nuclei showed a high level of agreement with a mean relative discrepancy of - 2.3 ± 5.5%. The Huntington's disease group showed significantly lower volumes in a variety of supratentorial brain structures. The highest degree of atrophy was shown for the caudate nucleus, putamen, and pallidum (all p < .0001). The caudate nucleus volume and the ratios were found to be strongly correlated in both groups. In conclusion, in patients with progressed Huntington's disease, it was shown that the automatically determined caudate nucleus volume correlates strongly with measured ratios commonly used in clinical practice. Both methods allowed clear differentiation between groups in this collective. The software additionally allows radiologists to more objectively assess the involvement of a variety of brain structures that are less accessible to standard semiquantitative methods., (© 2024. The Author(s).)

Background: Aging is a non-modifiable risk factor for neurodegenerative disease. It is well established that the brain undergoes physiological atrophy with age. So, this study was conducted to analyse the correlation between the age of the person and the size of the various subcortical nuclei of the brain and whether these measurements can serve as a useful indicator for physiological atrophy leading to degenerative disease in clinical practice., Methods: A total of 600 MRI scans from healthy individuals were examined and the measurements of subcortical nuclei were taken and subsequently analysed., Results: A statistically significant difference between the genders was observed in the sizes of the axial diameters of caudate nucleus, putamen and globus pallidus. Caudate nucleus transverse diameter showed a moderate negative correlation with age in males. Globus pallidus axial diameter with age showed weak positive correlation for males. Globus pallidus transverse diameter showed weak positive correlation with age for both males and females, but it was stronger for males compared to females., Conclusions: These results will help neurologists and neurosurgeons in analysing various early degenerative diseases and treat them accordingly., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Dhamija A et al.)

Mindfulness training has been shown to improve psychological health and general well-being. However, it is unclear which brain and personality systems may be affected by this practice for improving adaptive behavior and quality of life. The present study explores the effects of a 5-week mindfulness-based intervention (MBI) at the neuroanatomical level and its relationship with dispositional mindfulness and impulsivity. Sixty-six risky drivers were quasi-randomly assigned to a mindfulness training group (MT) or a control group (N). Participants underwent magnetic resonance imaging and completed the Five Facet Mindfulness Questionnaire (FFMQ) and the UPPS-P impulsivity scale twice, at baseline and after receiving the MBI. We observed that MBI changes dispositional mindfulness in the non-reactivity and observing facets. Further, we observed that the magnitude of change in impulsivity was associated with the change in dispositional mindfulness. Whole-brain voxel-wise analysis revealed that the volume of the right caudate nucleus of the MT group (n = 27) showed a reduction compared to that of the control group (n = 33), which increased in terms of the pre-post measurement (MT=-1.76 mm 3 ; N = 6.31 mm 3 ). We also observed that reduced caudate nucleus volume correlated with decreased positive urgency in the MT group. Taken together, our results show that MBI improves the skills of observing and non-reactivity to inner experience, while producing changes in the structure of the caudate nucleus. These structural changes are associated with a reduction in impulsivity levels, decreasing the tendency to act rashly in situations that generate positive emotions and thus facilitating more adaptive behavior., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

During task-based functional magnetic resonance imaging (t-fMRI) patients with depressive disorder (DD) have shown abnormal caudate nucleus activation. There have been no meta-analyses that are conducted on the caudate nucleus using Activation Likelihood Estimation (ALE) in patients with DD, and the relationships between abnormal caudate activity and different behavior domains in patients with DD remain unclear. There were 24 previously published t-fMRI studies included in the study with the caudate nucleus as the region of interest. Meta-analyses were performed using the method of ALE. Included five ALE meta-analyses: (1) the hypoactivated caudate nucleus relative to healthy controls (HCs); (2) the hyper-activated caudate nucleus; (3) the abnormal activation in the caudate nucleus in the emotion domain; (4) the abnormal activation in cognition domain; (5) the abnormal activation in the affective cognition domain. Results revealed that the hypo-/hyper-activity in the caudate subregions is mainly located in the caudate body and head, while the relationships between abnormal caudate subregions and different behavior domains are complex. The hypoactivation of the caudate body and head plays a key role in the emotions which indicates there is a positive relationship between the decreased caudate activity and depressed emotional behaviors in patients with DD., Competing Interests: Declaration of Competing Interest All authors of this paper declare that they have no potential conflict of interest, financial or otherwise, related directly or indirectly to this work., (Copyright © 2023. Published by Elsevier B.V.)

Background: Musculoskeletal (MSK) pain affects over 80% of People with Parkinson's (PD, PwP) and may, in part, be dopaminergic in origin, as dopaminergic medication often leads to its relief., Methods: PwP who underwent striatal dopamine transporter visualization with a radiopharmaceutical DaTscan™ ( 123 I-Ioflupane Injection) using a single-photon emission computed tomography (SPECT) as a part of their clinical-diagnostic work up were enrolled in the "Non-motor International Longitudinal Study" (NILS; UK National Institute for Health Research Clinical Research Network Number 10084) and included in this cross-sectional analysis. The association between specific DaTscan binding ratios for each striatum, the caudate nucleus and putamen and clinical ratings for MSK pain (assessed using the King's Parkinson's Disease Pain Scale (KPPS)) were analysed., Results: 53 PwP (30.2% female; age: 63.79 ± 11.31 years; disease duration (DD): 3.32 (0.31-14.41) years; Hoehn & Yahr stage (H&Y): 2 (1-4); Levodopa Equivalent Daily Dose (LEDD): 543.08 ± 308.94 mg) were assessed and included in this analysis. MSK pain was highly prevalent (71.7% of all participants, mean KPPS Item 1 score 5.34 ± 4.76) and did not correlate with the motor symptoms burden (SCOPA-Motor total score; p = 0.783) but showed a significant correlation with quality of life (PDQ-8, r s  = 0.290, p = 0.035). z-scores for the caudate nucleus (Exp (B) = 0.367, 95% CI for Exp (B) 0.148-0.910, p = 0.031) and striatum (Exp (B) = 0.338, 95% CI for Exp (B) 0.123-0.931, p = 0.036), adjusted for DD, H&Y and LEDD, were significant determinants of MSK pain., Conclusions: Our findings suggest an association between MSK pain in PwP and the severity of dopaminergic deficiency in the caudate nucleus., Significance: In People with Parkinson's, musculoskeletal pain does not arise simply as a direct sequel to motor symptoms-instead, it is linked to the severity of dopaminergic depletion in the caudate nucleus., (© 2023 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Abstract: Frontotemporal dementia is a clinical syndrome that is characterized by a progressive deterioration in behavior, personality, and/or language, with relative preservation of memory, and its phenotype and molecular basis are heterogeneous. We present a case of a 62-year-old female patient who underwent 18 F-FDG PET/CT and 18 F-FP-CIT PET/CT for differential diagnosis of psychiatric disease and types of dementia. 18 F-FDG PET/CT image showed a compatible finding for frontotemporal dementia, and 18 F-FP-CIT PET/CT image showed dominantly decreased dopamine transporter activity in the bilateral caudate nucleus., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Huntington's Disease Integrated Staging System (HD-ISS) defined disease onset using volumetric cut-offs for caudate and putamen derived from FreeSurfer 6 (FS6). The impact of the latest software update (FS7) on volumes remains unknown. The Huntington's Disease Young Adult Study (HD-YAS) is appropriately positioned to explore differences in FS bias when detecting early atrophy., Objective: Explore the relationships and differences between raw caudate and putamen volumes, calculated total intracranial volumes (cTICV), and adjusted caudate and putamen volumes, derived from FS6 and FS7, in HD-YAS., Methods: Images from 123 participants were segmented and quality controlled. Relationships and differences between volumes were explored using intraclass correlation (ICC) and Bland-Altman analysis., Results: Across the whole cohort, ICC for raw caudate and putamen was 0.99, cTICV 0.93, adjusted caudate 0.87, and adjusted putamen 0.86 (all p < 0.0005). Compared to FS6, FS7 calculated: i) larger raw caudate (+0.8%, p < 0.00005) and putamen (+1.9%, p < 0.00005), with greater difference for larger volumes; and ii) smaller cTICV (-5.1%, p < 0.00005), with greater difference for smaller volumes. The systematic and proportional difference in cTICV was greater than raw volumes. When raw volumes were adjusted for cTICV, these effects compounded (adjusted caudate +7.0%, p < 0.00005; adjusted putamen +8.2%, p < 0.00005), with greater difference for larger volumes., Conclusions: As new software is released, it is critical that biases are explored since differences have the potential to significantly alter the findings of HD trials. Until conversion factors are defined, the HD-ISS must be applied using FS6. This should be incorporated into the HD-ISS online calculator.

We have investigated dogs' (Canis familiaris) abilities in associating different sounds with appetitive stimuli of different incentive values. The association's establishment was first tested on family dogs (n = 20) in a problem-solving behavioural paradigm (experiment 1), then in a problem-solving behavioural paradigm as well as an fMRI study on specially trained family dogs (n = 20) (experiment 2). The aim was to show behavioural and parallel neural effects of the association formed between the two sounds and two different associated appetitive stimuli. The latency of solving the problem was considered an indicator of the motivational state. In our first experiment, where only behaviour was studied, we found that dogs were quicker in solving a problem upon hearing the sound associated with food higher in reward value, suggesting that they have successfully associated the sounds with the corresponding food value. In our second experiment, this behaviour difference was not significant. In the fMRI study, the cerebral response to the two sounds was compared both before and after the associative training. Two bilateral regions of interest were explored: the caudate nucleus and the amygdala. After the associative training, the response in the caudate nucleus was higher to the sound related to a higher reward value food than to the sound related to a lower reward value food, which difference was not present before the associative training. We found an increase in the amygdala response to both sounds after the training. In a whole-brain representational similarity analysis, we found that cerebral patterns in the caudate nucleus to the two sounds were different only after the training. Moreover, we found a positive correlation between the dissimilarity index in the caudate nucleus for activation responses to the two sounds and the difference in latencies (i.e. high reward value associated sound condition latency-low reward value associated sound condition latency) to solve the behavioural task: the bigger the difference between the conditions in latency to solve the task, the greater the difference in the neural representation of the two sounds was. In summary, family dogs' brain activation patterns reflected their expectations based on what they learned about the relationship between two sounds and their associated appetitive stimuli., (© 2023. Springer Nature Limited.)

Background: Apathy is common in multiple sclerosis (MS) and neurological disease, but its presence and underlying brain mechanisms in older adults with MS (OAMS) have not been evaluated., Objective: Examine apathy and its association with caudate nuclei volume in OAMS and controls. We hypothesized that compared to controls, OAMS would demonstrate: a) greater apathy; b) stronger associations between apathy and caudate nuclei volumes., Methods: OAMS ( n = 67, mean age = 64.55 ± 3.89) and controls ( n = 74, mean age = 69.04 ± 6.32) underwent brain MRI, cognitive assessment, psychological, and motoric testing. Apathy was assessed through the apathy subscale of the 30-item Geriatric Depression Scale., Results: OAMS reported greater apathy compared to controls ( β = 0.281, p = 0.004). Adjusted moderation analyses revealed a significantly stronger association between caudate volume and apathy (left: B = -1.156, p = 0.039, right: B = -1.163, p = 0.040) among OAMS compared to controls. Conditional effects revealed that in adjusted models, lower volume of both the left ( b = -0.882, p = 0.037) and right ( b = -0.891, p = 0.038) caudate nuclei was significantly associated with greater apathy only among OAMS., Conclusion: Caudate nuclei, which are susceptible to adverse MS effects and implicated in mediating cognitive and motor function, may influence the presence and severity of apathy in OAMS.

Structural grey and white matter changes precede the manifestation of clinical signs of Huntington's disease by many years. Conversion to clinically manifest disease therefore likely reflects not merely atrophy but a more widespread breakdown of brain function. Here, we investigated the structure-function relationship close to and after clinical onset, in important regional brain hubs, particularly caudate nucleus and putamen, which are central to maintaining normal motor behaviour. In two independent cohorts of patients with premanifest Huntington's disease close to onset and very early manifest Huntington's disease (total n = 84; n = 88 matched controls), we used structural and resting state functional MRI. We show that measures of functional activity and local synchronicity within cortical and subcortical regions remain normal in the premanifest Huntington's disease phase despite clear evidence of brain atrophy. In manifest Huntington's disease, homeostasis of synchronicity was disrupted in subcortical hub regions such as caudate nucleus and putamen, but also in cortical hub regions, for instance the parietal lobe. Cross-modal spatial correlations of functional MRI data with receptor/neurotransmitter distribution maps showed that Huntington's disease-specific alterations co-localize with dopamine receptors D1 and D2, as well as dopamine and serotonin transporters. Caudate nucleus synchronicity significantly improved models predicting the severity of the motor phenotype or predicting the classification into premanifest Huntington's disease or motor manifest Huntington's disease. Our data suggest that the functional integrity of the dopamine receptor-rich caudate nucleus is key to maintaining network function. The loss of caudate nucleus functional integrity affects network function to a degree that causes a clinical phenotype. These insights into what happens in Huntington's disease could serve as a model for what might be a more general relationship between brain structure and function in neurodegenerative diseases in which other brain regions are vulnerable., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Memory retrieval effects in the striatum are well documented and robust across experimental paradigms. However, the functional significance of these effects, and whether they are moderated by age, remains unclear. We used functional magnetic resonance imaging paired with an associative recognition task to examine retrieval effects in the striatum in a sample of healthy young, middle-aged, and older adults. We identified anatomically segregated patterns of enhanced striatal blood oxygen level-dependent (BOLD) activity during recollection- and familiarity-based memory judgments. Successful recollection was associated with enhanced BOLD activity in bilateral putamen and nucleus accumbens, and neither of these effects were reliably moderated by age. Familiarity effects were evident in the head of the caudate nucleus bilaterally, and these effects were attenuated in middle-aged and older adults. Using psychophysiological interaction analyses, we observed a monitoring-related increase in functional connectivity between the caudate and regions of the frontoparietal control network, and between the putamen and bilateral retrosplenial cortex and intraparietal sulcus. In all instances, monitoring-related increases in cortico-striatal connectivity were unmoderated by age. These results suggest that the striatum, and the caudate in particular, couples with the frontoparietal control network to support top-down retrieval-monitoring operations, and that the strength of these inter-regional interactions is preserved in later life., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Dopamine transporter (DAT) PET provides higher resolution than DAT SPECT and opportunity for integrated imaging with MRI. The radioligand [ 18 F]FE-PE2I is highly selective for the DAT, and PET measurements with this radioligand have good reliability and repeatability in patients with non-advanced Parkinson's disease., Objectives: To validate [ 18 F]FE-PE2I PET as measurement tool of longitudinal DAT changes in patients with Parkinson's disease., Methods: Thirty-seven subjects with Parkinson's disease (Hoehn and Yahr stage < 3) were included in a longitudinal PET study with [ 18 F]FE-PE2I. DAT availability (BP ND ) in the caudate nucleus, putamen, sensorimotor striatum, and substantia nigra, was estimated with parametric imaging using Logan graphical analysis and cerebellum as reference region. For comparison with DAT-SPECT literature, sample size calculations for disease intervention studies were made., Results: Baseline and follow-up PET data (interval: 2.3 ± 0.5 years) were available for 25 patients (9 females, 16 males). Median age was 64.7 years (range 46-76); symptom duration: 3 years (0.25-14); Hoehn and Yahr stage (H&Y): 1 (1-2). Annualized DAT decline and effect size were: -8.5 ± 6.6 % and 1.08 for caudate nucleus; -7.1 ± 6.1 % and 1.02 for putamen; -8.3 ± 8.5 % and 0.99 for sensorimotor striatum; -0.11 ± 9.3 % and 0.11 for substantia nigra. The estimated minimum sample size needed for a treatment trial using [ 18 F]FE-PE2I PET as imaging marker is 2-3 times lower than is reported in literature on [ 123 I]FP-CIT SPECT., Conclusions: Longitudinal [ 18 F]FE-PE2I PET measurements in non-advanced PD demonstrate a striatal DAT decline consistent with previous SPECT and PET studies. No obvious changes of DAT availability were observed in the substantia nigra, indicating perhaps slower progression or compensatory changes. The effect sizes were numerically larger than reported in the literature for other DAT radioligands, suggesting that [ 18 F]FE-PE2I might detect smaller DAT changes, and can be well used as progression marker in clinical trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise. In contrast, there were overall smaller differences in behavioral and neural modulation by drift surprise. Our results suggest that the impact of dopamine-relevant polymorphisms in the flexibility-stability trade-off may result in part from the role of dopamine in encoding the weight afforded to events requiring updating or stabilization., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The definitive pathogenic mechanisms underlying chronic migraine (CM) remain unclear. Mounting evidence from functional and structural magnetic resonance imaging (MRI) studies suggests that the caudate nucleus (CN) plays a role in the cognitive, sensory, and emotional integration of pain information in patients with migraine. However, evidence concerning the role played by CN in CM patients is limited. Here, we used the CN as the seed to explore patterns of functional connectivity (FC) among healthy controls (HCs), patients with episodic migraine (EM), and patients with CM., Methods: We included 25 HCs, 23 EM patients, and 46 CM patients in this study. All participants underwent resting-state functional MRI scans on a GE 3.0T MRI system. We performed seed-based FC analyses among the three groups using the bilateral CNs as seeds. We also compared the subgroups of CM (with and without medication overuse headache, males and females) and performed Pearson's correlation analyses between FC values and the clinical features of CM patients., Results: FC values between the right CN and five clusters (mainly involved in emotion, cognition, and sensory-related brain regions) were higher in CM patients than in HCs. Compared to EM patients, enhanced FC values between the bilateral precuneus, left anterior cingulate gyrus, right middle cingulate cortex, right lingual gyrus, and right CN were shown in the CM patients. There were no significant differences between CM patients with and without MOH, males and females. FC values between the bilateral calcarine cortex, lingual gyrus, and right CN were positively correlated with body mass index. Moreover, right CN-related FC values in the left calcarine cortex and right lingual gyrus were inversely correlated with visual analogue scale scores for headaches., Conclusion: Our results revealed abnormal right CN-based FC values in CM patients, suggesting dysfunction of brain networks associated with pain perception and multi-regulation (emotion, cognition, and sensory). Aberrant FC of the CN can provide potential neuroimaging markers for the diagnosis and treatment of CM., (© 2022. The Author(s).)

The ineligible role of the caudate nucleus in sleep has been implicated. Previous literature showed that the caudate volume is associated with longer habitual sleep duration in older adults. However, the association between sleep duration and caudate volume remains unknown in the younger population. In this study, we examined the caudate volume in youth to older adults (10 to 85 years old) with a greater sample size (N = 464). The volumetric size of the caudate nucleus showed significantly positive association with habitual sleep duration, especially in younger population. Sleep duration showed a significant association with executive function performance. However, caudate volume did not significantly predict executive function. Our results suggested that sleep duration is associated with the caudate volume and executive function. It is also suggested that there are some external mechanisms that modulate executive function which prevent the caudate-sleep relation's effect on executive function., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neurological complications are frequently mentioned in the published reports regarding the coronavirus disease 2019 (COVID-19). Especially encephalopathy draws attention as the leading symptom or complication of COVID-19 in some reports. This article discussed a 3-year-old patient with bilateral lentiform and caudate nuclei involvement on brain imaging, who presented with mental status changes and acute muscular weakness, possibly due to COVID-19. To the best of our knowledge, this case is the first one showing pathological signal enhancement and edema in bilateral lentiform and caudate nuclei associated with COVID-19., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

The morphological development of the fetal striatum during the second trimester has remained poorly described. We manually segmented the striatum using 7.0-T MR images of the fetal specimens ranging from 14 to 22 gestational weeks. The global development of the striatum was evaluated by volume measurement. The absolute volume (Vabs) of the caudate nucleus (CN) increased linearly with gestational age, while the relative volume (Vrel) showed a quadratic growth. Both Vabs and Vrel of putamen increased linearly. Through shape analysis, the changes of local structure in developing striatum were specifically demonstrated. Except for the CN tail, the lateral and medial parts of the CN grew faster than the middle regions, with a clear rostral-caudal growth gradient as well as a distinct "outside-in" growth gradient. For putamen, the dorsal and ventral regions grew obviously faster than the other regions, with a dorsal-ventral bidirectional developmental pattern. The right CN was larger than the left, whereas there was no significant hemispheric asymmetry in the putamen. By establishing the developmental trajectories, spatial heterochrony, and hemispheric dimorphism of human fetal striatum, these data bring new insight into the fetal striatum development and provide detailed anatomical references for future striatal studies., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a treatable neurometabolic disease caused by variants in SLC19A3. Typical imaging features include symmetrical involvement of the caudate nuclei and putamina., Objective: The study sought to explore classical BTBGD without caudate nucleus involvement, to highlight the importance of recognizing this new pattern early in the disease., Methods: Individuals with genetically confirmed BTBGD who harbored the same homozygous variant: NM&#95;025243.4 (SLC19A3): c.1264A > G (p.Thr422Ala) and had atypical neuroimaging were recruited., Results: Nine patients with BTBGD had atypical neuroimaging findings on the first MRI scan. The median age at symptom onset was 3 years. All patients presented with classical clinical features of subacute encephalopathy, dystonia, ataxia, and seizures. During the acute crisis, MRI revealed bilateral and symmetric involvement of the putamina in all patients; one showed small caudate nuclei involvement. In addition, the thalami, cerebellum, and brain stem were involved in six patients, seven patients, and three patients, respectively. Treatment included a combination of high doses of thiamine and biotin. One patient died; he did not receive any vitamin supplementation. Two patients who were treated late had severe neurological sequelae, including generalized dystonia and quadriplegia. Six patients treated early had good outcomes with minimal sequelae, including mild dystonia and dysarthria. Two patients showed the classical chronic atrophic and necrotic changes already described., Conclusion: The early atypical neuroimaging pattern of BTBGD described here, particularly the lack of caudate nucleus involvement, should not dissuade the clinician and radiologist from considering a diagnosis of BTBGD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Impaired decision making, a key characteristic of alcohol dependence (AD), manifests in continuous alcohol consumption despite severe negative consequences. The neural basis of this impairment in individuals with AD and differences with known neural decision mechanisms among healthy subjects are not fully understood. In particular, it is unclear whether the choice behavior among individuals with AD is based on a general impairment of decision mechanisms or is mainly explained by altered value attribution, with an overly high subjective value attributed to alcohol-related stimuli., Methods: Here, we use a functional magnetic resonance imaging (fMRI) monetary reward task to compare the neural processes of model-based decision making and value computation between AD individuals (n = 32) and healthy controls (n = 32). During fMRI, participants evaluated monetary offers with respect to dynamically changing constraints and different levels of uncertainty., Results: Individuals with AD showed lower activation associated with model-based decision processes in the caudate nucleus than controls, but there were no group differences in value-related neural activity or task performance., Conclusions: Our findings highlight the role of the caudate nucleus in impaired model-based decisions of alcohol-dependent individuals., (© 2022 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)

Ample studies have reported a strong association between emotion and subcortical volumes; still, the underlying mechanism regarding this relation remains unclear. Using a twin design, the current study aimed to explore the intrinsic association between emotion and subcortical volumes by examining their phenotypic, genetic, and environmental correlations. We used a group dataset of 960 individuals from the Human Connectome Project (234 monozygotic twins, 145 dizygotic twins, 581 not twins, males = 454, age = 22-37 years). We found that both emotion and subcortical volumes were heritable. Of the 17 emotional traits, 13 were significantly phenotypically correlated with the volumes of multiple subcortical regions. There was no environmental correlation between emotion and subcortical volumes; however, we found a genetic overlap between overall emotional traits and caudate volume. Taken together, our results showed that emotion and subcortical volumes were heritable and closely related. Although the caudate has been often studied with execution of movement, given that the caudate volume is genetically associated with diverse emotional domains, such as negative affect, psychological well-being, and social relationships, it may suggest that the caudate volume might also be an important factor when studying the brain basis of emotion., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The inverse base rate effect (IBRE) is a nonrational behavioral phenomenon in predictive learning. Canonically, participants learn that the AB stimulus compound leads to one outcome and that AC leads to another outcome, with AB being presented three times as often as AC. When subsequently presented with BC, the outcome associated with AC is preferentially selected, in opposition to the underlying base rates of the outcomes. The current leading explanation is based on error-driven learning. A key component of this account is prediction error, a concept previously linked to a number of brain areas including the anterior cingulate, the striatum, and the dorsolateral prefrontal cortex. The present work is the first fMRI study to directly examine the IBRE. Activations were noted in brain areas linked to prediction error, including the caudate body, the anterior cingulate, the ventromedial prefrontal cortex, and the right dorsolateral prefrontal cortex. Analyzing the difference in activations for singular key stimuli (B and C), as well as frequency matched controls, supports the predictions made by the error-driven learning account., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross-sectional 2-by-2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high-field 7.0 T resting-state fMRI. The second study was a pilot case-control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting-state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks-dorsal caudate head with Heschl's gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case-series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The study of greed has been broadly investigated and discussed in the field of social sciences, including economics, political science, and psychology. However, the neural mechanisms underlying greed personality trait (GPT) have received little attention from the cognitive neuroscience field and still remain unclear. In this study, we explored the associations between GPT and static/dynamic reward circuit-specifically its sub-regions' functional networks including caudate, nucleus accumbens (NAcc), and putamen. Behavioral analyses revealed significant associations of GPT with Past-Negative and Present-Fatalistic time attitude as well as attention impulsivity. Imaging analyses revealed a significant interaction effect between sex and GPT on the static reward functional networks. In particular, GPT was positively correlated with static caudate-NAcc, caudate-cerebellum, and NAcc-parahippocampus/medial orbitofrontal cortex (PHG/mOFC) for males but negatively correlated for females. GPT was also marginally and negatively correlated with static putamen-occipital pole functional connectivities among males. Interestingly, sex difference interaction patterns were further observed in the dynamic reward functional networks. Further, dynamic reward functional networks also exhibited some specific characteristics, manifesting in more brain regions involved for greedy behaviors. These findings suggest sex-specific static and dynamic functional networks underlying human dispositional greed, and also implicate the critical contributions of reward circuit, especially for sub-circuits of reward, on greed., (Copyright © 2021. Published by Elsevier Ltd.)

The act of punishing unfair behavior by unaffected observers (i.e., third-party punishment) is a crucial factor in the functioning of human societies. In everyday life, we see different types of individuals who punish. While some individuals initiate costly punishment against an unfair person independently of what other observers do (independent punishers), others condition their punishment engagement on the presence of another person who punishes (conditional punishers). Still others do not want to partake in any sort of punishment (nonpunishers). Although these distinct behavioral types have a divergent impact on human society, the sources of heterogeneity are poorly understood. We present novel laboratory evidence on the existence of these three types. We use anatomical brain characteristics in combination with stated motives to characterize these types. Findings revealed that independent punishers have larger gray matter volume in the right temporo-parietal junction compared to conditional punishers and nonpunishers, an area involved in social cognition. Conditional punishers are characterized by larger gray matter volume in the right dorsolateral prefrontal cortex, a brain area known to be involved in behavioral control and strategic reasoning, compared to independent punishers and nonpunishers. Finally, both independent punishers and nonpunishers are characterized by larger gray matter volume in an area involved in the processing of social and monetary rewards, that is, the bilateral caudate. By using a neural trait approach, we were able to differentiate these three types clearly based on their neural signatures, allowing us to shed light on the underlying psychological mechanisms., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The organization of socio-cognitive processes is a multifaceted problem for which many sophisticated concepts have been proposed. One of these concepts is social intelligence (SI), i.e., the set of abilities that allow successful interaction with other people. The theory of mind (ToM) human brain network is a good candidate for the neural substrate underlying SI since it is involved in inferring the mental states of others and ourselves and predicting or explaining others' actions. However, the relationship of ToM to SI remains poorly explored. Our recent research revealed an association between the gray matter volume of the caudate nucleus and the degree of SI as measured by the Guilford-Sullivan test. It led us to question whether this structural peculiarity is reflected in changes to the integration of the caudate with other areas of the brain associated with socio-cognitive processes, including the ToM system. We conducted seed-based functional connectivity (FC) analysis of resting-state fMRI data for 42 subjects with the caudate as a region of interest. We found that the scores of the Guilford-Sullivan test were positively correlated with the FC between seeds in the right caudate head and two clusters located within the right superior temporal gyrus and bilateral precuneus. Both regions are known to be nodes of the ToM network. Thus, the current study demonstrates that the SI level is associated with the degree of functional integration between the ToM network and the caudate nuclei., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Votinov, Myznikov, Zheltyakova, Masharipov, Korotkov, Cherednichenko, Habel and Kireev.)